1. FIELD OF THE INVENTION
The present invention relates to a method of diagnosing impaired blood flow in an organ using in vivo imaging.
2. DESCRIPTION OF RELATED ART
In recent years the use of various contrast agents for non-invasive diagnostic imaging has become routine. In parallel with this increased use has come improvements in both the quality and diversity of instruments used for detection, as well as the development of new contrast agents for use with these various instruments. The search for the ideal agents for use in diagnostic imaging has focused on agents with static distribution where uptake is relative to some functional parameter such as blood flow, metabolic rate, or receptor density. Static biodistribution is particularly important when the diagnostic instrument is based on single photon emission computed tomography (SPECT), since the vast majority of SPECT imaging devices require about 20-30 minutes for image acquisition, during which time little change in contrast agent distribution can occur. Consequently, agents that lack a static distribution have been systematically discarded for measuring regional blood perfusion. This is particularly true of technetium or iodine radiolabeled compounds for measurement of blood flow in the heart or the brain.
Present tests for diagnostic imaging which measure regional organ perfusion can be divided into three broad categories: those which are based upon the administration of a contrast agent which is distributed relative to blood flow, without further change; those based upon the administration of an inert gas; and those based upon the administration of positron-labelled physiological radiotracers.
The use of contrast agents which are distributed relative to blood flow in the absence of further change, such as .sup.99m Tc-HMPAO (hexamethyl propyleneamine oxime) for brain imaging and .sup.99m Tc-isonitriles for myocardial imaging, have significant draw-backs. For example, when asymmetries occur, it is difficult to distinguish between areas of potentially increased blood flow and areas of decreased blood flow. As a consequence, it is difficult to discern whether one area is increased or whether the adjacent area is decreased.
The use of inert gas also presents significant difficulties. The typically utilized gas, xenon, is difficult to administer and imaging with this agent provides very limited spatial resolution. In addition, this technique has never been shown to be capable of detecting coronary artery disease at rest.
The administration of positron-labelled physiological radiotracers as contrast agents, such as .sup.13 N-ammonia or .sup.15 O-water, require on-site cyclotron production and radiochemical preparation and can only be imaged using a positron emission tomograph (PET) scanner which is not available in many nuclear medicine laboratories. This technique has also never been shown to be capable of detecting coronary artery disease at rest.
One area where there has been considerable interest in the use of contrast agents has been for the detection of coronary artery disease using myocardial perfusion scintigraphy. At the present time the primary agent used for such diagnosis is .sup.201 thallous chloride. Unfortunately, this agent presents significant disadvantages in that it has a long physical half-life, poor imaging characteristics, complicated biokinetics in the heart, and high cost. Another group of agents which are used, the isonitriles, do not redistribute, that is, show a relative increase in regional myocardial concentration in a lesion from the images recorded initially to the images recorded later, and require separate stress and rest injections over at least a 4 hour period.
A major drawback associated with many of the agents presently used is that they require exercise stress testing for the detection of coronary artery disease thereby creating a situation which is potentially dangerous to patients with cardiac disease. As a consequence, such agents can only be used at a limited level with patients recovering from acute myocardial infarction. In addition, many patients, such as those recovering from major surgery, or are handicapped, cannot exercise adequately to undergo the stress testing regimen.
A group of drugs which has been of interest in the area of myocardial perfusion scintigraphy are the boronic acid adducts of technetium dioxime, or BATO agents (U.S. Pat. Nos. 4,705,849; 4,714,605). However, it had been believed that even these agents required testing under conditions of stress and non-stress. (Seldin, et al., The Journal of Nuclear Medicine, 30:312, 1989).
Consequently, a considerable need exists for a method of evaluating impaired blood flow in an organ of a patient which will allow the patient to remain at rest, which can be performed in a shorter period of time, and which requires only one injection of the contrast agent.